Plant genomes, animal genomes, more and more genomes!

I recently returned from the Plant and Animal Genome Conference (XVI, Jan. 12-16, in San Diego). This conference is much more applied than what I'm used to, but I came because it seemed a good place to see comparative genomics in full bloom, and that turned out to be true. I was struck by the extent to which the meeting was a showcase for vendors (Agilent, Sequenom, BioTrove, Illumina, Roche (now incorporating 454 and Nimblegen), Affymetrix, Applied Biosystems, Keygene, etc.), many of whom literally wined and dined conferees at their workshops.

However, I was also struck by the extent to which new high-throughput sequencing technologies are already in widespread use. Ronan O'Malley (Ecker lab) described the sequencing of Cvi, a strain of Arabidopsis distinct from the Columbia accession already determined; in the process he compared 454 and Solexa sequencing. Steve Jacobson (UCLA) described the repeated re-sequencing of (bisulfite-modified) Columbia for the purpose of studying cytosine methylation. Several more plant genomes are in in the pipeline, and a sense of the pace is conveyed by the fact that plenary speaker Eddy Rubin (JGI) "announced" the completion of the soybean genome almost in passing.

Other plenary talks were uniformly excellent. I missed the initial talk, by Jerry Caulder, which was apparently quite controversial. David Baulcombe referred to it by saying that the European perspective on genetically modified foods is different and that "by shying away from the hazards we don't gain credibility." Another notable aside was Michael Ashburner's statement that "there is no point in funding biomedical research unless you also fund informatics."

This week, it's ancestry

Last weekend there was a lot of buzz about personal genomics (see Genome Technology Daily, "It was a Helluva Weekend for Personal Genomics"; or Eye on DNA, "DNA Network Members Discuss Personal Genomics Service Providers 23andMe, deCODEme, and Navigenics"; or my previous post). This weekend, it's ancestry. Today's papers had two interesting features on ancestry testing, both of which nicely echoed my own post about caution regarding ancestry testing ("On Genes"). First, the New York Times business section ("DNA Tests Find Branches but Few Roots") discusses the business of ancestry testing. The article is nice in that it compares the cost of ancestry testing by various companies, shows that results differ, and quotes Henry Louis Gates Jr. making reasoned assessments of the role that DNA testing can play. Second, the Washington Post reviews "The Genetic Strand: Exploring a Family History Through DNA" by Edward Ball("Blue Blood, Black Genes").

The theme is clear. You can only learn so much about your ancestors from DNA.

Ready or not, personalized genetics is here.

Yesterday's announcement by deCODE genetics that they would be launching a personalized genetics service, deCODEme (news release), means that a major player in gene discovery has just joined the growing field of companies offering personalized genetic services. As I wrote in my Nature Network blog, "On Genes" in "The Scientist Blogger and the Personal Genome," information about susceptibility to disease, potential for health or accomplishment and responsiveness to therapies is found in our genes, and it is going to be made available to people who want it. A lot of people are going to want it. Most are not going to be prepared to understand it. Even Jim Watson and J. Craig Venter aren't entirely sure what to make of their genomes. Genetic counseling may morph into a profession that serves everyone, not just those who faced with clear cases of genetic disease.

Journalists and scientists also have a role to play. Let me highlight three useful responses.

The New York Times has an excellent series called "The DNA age." These articles (all by Amy Harmon, at least so far), "explore the impact of new genetic technology on American life." One published today, "My Genome, Myself: Seeking Clues in DNA" describes her use of the 23andMe service.

Bertalan Meskó, a blogger at "ScienceRoll," presents coverage of Personalized Medicine, including a summary of breaking news (today) and a review of services offered by Navigenics, 23andMe and Helix Health (last week, before the deCODE announcement).

I have started "Information on Genes," (ongenes), a web site that is intended to be a place where answers to questions on genes, genetics and genomics are provided by experts in the field. Questions will be posted anonymously but answers will not. I plan to solicit answers from people in the know. My hope is that ongenes will provide useful information to anyone trying to understand genetic tests, including professionals in the field.

Simons Foundation funds research on sporadic autism mutations

Because I've dealt with the issue of sporadic autism linked to paternal age before (links) it seems worthwhile noting here that the Rutgers University Cell and DNA Repository will use a $7.8 million grant from the Simons Foundation to establish a new collection of DNA samples to help autism researchers study sporadic germ-line mutations. This story is covered by GenomeWeb today.

'On Genes," my blog on Nature Network

After commenting on Nature Network ("What's up with Nature?"), I ended up creating a new blog over there. It's "On Genes," and the URL is network.nature.com/blogs/user/smount. It's not clear what I'll put there as opposed to here. Perhaps one of the two blogs will die. Right now, the plan is to put more substantial scientific posts here and more news-oriented posts there.

Along those lines, my first real post on the Nature Network blog, "PRISM distorts our view of the open access debate" was in response to Jonathan Eisen's blog entry “PRISM – Partnership for Research Integrity in Science and Medicine – Seems like a spoof but it is real, and sad“). It makes me angry to see issues that concern me be taken up by a public relations firm that is so thoroughly dishonest. But I won't repeat that here. You can read about it there.

Plants, Animals and the Ancient RNA Toolkit

Multicellularity has arisen independently several times, but most famously twice, in the two lineages giving rise to plants and animals. In fact, the last unicellular ancestors of these two lineages were not particularly closely related, and the last common ancestor of both plants and animals also gave rise to an enormous number of extant unicellular progeny, including all of the fungi. When I began serious work on the regulation of pre-mRNA splicing in plants in 2001 I did so with an awareness of how very similar the process is to pre-mRNA splicing in animals. This is all the more striking because so many species have lost this complexity. In fact, plants and animals share many processes that must have been present in the last common ancestor, but have been lost in many unicellular eukaryotes derived from that same ancestory. RNA figures heavily in the list, which includes microRNAs, U12 introns, the exon junction complex and complex alternative splicing.

Although the last common ancestor of plants and animals was almost certainly much more complex than most modern unicellular eukaryotes (at least in terms of its genome), it was probably not multicellular. The signals that control development in animals (wnts, hedgehog, FGFs, TGF-betas, etc.) are completely missing in plants. Likewise, the genes involved in meristem maintenance, ethylene-signaling, auxin-signaling and so on are missing in animals. It's also worth pointing out that the opisthokont clade (which includes animals and the fungi) is well-established (see the figure, which is from the Tree of Life Web Project).

Perhaps most convincing are the exceptions: the processes shared by animals and plants but missing from most unicellular eukaryotes are not missing from all. U12 introns were recently found in distantly related protists and in a fungus (see my comment). MicroRNAs were recently described in Chlamydomonas reinhardtii, a unicellular green alga (Zhao et al., 2007). There is even a miRNA family that is appears to be conserved between plants and animals and targets a homologous family of splicing regulators (Arteaga-Vazquez et al. 2006).

It is therefore frustrating to read commentaries that are written as though genomic complexity is new. For example, Ram and Ast (2007) mistakenly generalize from S. cerevisiae to S. pombe (which retains more genomic complexity of several sorts, including alternative splicing) and talk about "before and after" incorrectly. Their conclusion, that "SR proteins had already facilitated the splicing of weak introns before the evolution of alternative splicing" may be correct, but complex alternative splicing was almost certainly present in the last common ancestor of plants and animals. I say this based on the fact that it had many genes whose products function in the regulation of alternative splicing, and which have been lost in unicellular descendants lacking complex alternative splicing (among these is a repertoire of at least four SR proteins).

What is most interesting to me is the correlation between developmental complexity and retention of genomic complexity, including alternative splicing and miRNAs. It might not have evolved with multicellularity, but the ancient RNA toolkit might be very useful when it comes to building a complex organism.